title: Interleukin-2-based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients.
abstract: OBJECTIVE
  This article analyzes the long-term results of 203 consecutive patients with metastatic renal cell carcinoma who were treated with various recombinant interleukin-2 (rIL-2) -based immunotherapy regimens, and describes factors that may influence response to therapy and long-term survival.
  
  
  METHODS
  The response and survival of 203 patients with metastatic renal cell carcinoma treated consecutively between July 1987 and October 1995 at the UCLA Medical Center Kidney Cancer Program with rIL-2-based immunotherapy were analyzed. Patients were divided into four groups: (1) no prior nephrectomy (n = 24), (2) nephrectomy > 6 months prior to rIL-2 therapy (n = 76), (3) nephrectomy < or = 6 months prior to rIL-2 therapy (n = 47), and (4) nephrectomy followed by treatment with rIL-2 and tumor-infiltrating lymphocytes +/- interferon-alpha (n = 56). Response and survival for each of these patient groups and survival per response to therapy were compared.
  
  
  RESULTS
  The overall median survival for all patients was 18 months, and survival at 1, 2, and 3 years after therapy was 61%, 40%, and 31% percent, respectively. A total of 12 patients (6%) achieved a complete response, and all were alive at 3 years. Of 36 patients (18%) who achieved a partial response and 41 patients (20%) with stable disease, 3-year survival was 37% and 50%, respectively. The survival of patients with a partial response or stable disease was significantly better than that of patients who exhibited progressive disease. Patients with nephrectomy > 6 months prior to rIL-2 therapy had a 46% 3-year survival rate, compared with a 9% 3-year survival rate for patients with nephrectomy < or = 6 months prior to rIL-2 therapy and a 4% 3-year survival rate for patients with no nephrectomy. Patients treated with tumor-infiltrating lymphocytes had a 38% 3-year survival rate, which was also significantly better than patients treated with nephrectomy < or = 6 months prior to rIL-2 therapy or with no nephrectomy.
  
  
  CONCLUSIONS
  This analysis demonstrated that rIL-2-based therapy offers a significant survival benefit to patients with advanced metastatic renal cell carcinoma, compared with historical controls. Furthermore, we have shown that nephrectomy > 6 months prior to rIL-2 therapy and nephrectomy followed by treatment with tumor-infiltrating lymphocytes/rIL-2 +/- interferon-alpha was associated with the greatest survival benefit. Tumor response to rIL-2-based therapy and time from nephrectomy to treatment were the most important predictors of survival. Randomized studies in a large group of patients are needed to confirm these observations.
authors.affiliation: Department of Medicine, University of California at Los Angeles School of Medicine, USA.
authors.forename: R
authors.initials: R
authors.lastname: Figlin
authors.forename: B
authors.initials: B
authors.lastname: Gitlitz
authors.forename: J
authors.initials: J
authors.lastname: Franklin
authors.forename: F
authors.initials: F
authors.lastname: Dorey
authors.forename: N
authors.initials: N
authors.lastname: Moldawer
authors.forename: J
authors.initials: J
authors.lastname: Rausch
authors.forename: J
authors.initials: J
authors.lastname: deKernion
authors.forename: A
authors.initials: A
authors.lastname: Belldegrun
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D005472:Fluorouracil